Immunointervention therapy may be an effective therapy for individuals at the early stages of insulin dependent diabetes mellitus (IDDM). The appropriate target population for such therapy is those with a high risk of eventual progression to frank IDDM. Thus, immunogenetic markers allowing early identification of subjects who will progress to IDDM are important. We are studying autoantibodies to new and existing antigens, autoantibody isotypes, HLA genotypes, and peripheral blood T-lymphocyte assays, all as potential early markers of progression. Family studies show that persons with multiple autoantibodies and low beta cell function invariably progress to IDDM. However, the progression may take several years. Therefore we will use low beta cell function as a clinical endpoint. In a group of subjects who are autoantibody positive but with normal beta cell function we will prospectively monitor beta cell function and potential markers of subsequent progression to IDDM. Those who develop abnormal beta cell function will be compared with those who do not in regard to these markers.